European journal of nuclear medicine and molecular imaging · 2026
[18F]FAPI-42 PET/CT for prognostic assessment in idiopathic pulmonary fibrosis: a prospective head-to-head comparison with [18F]FDG PET/CT.
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Fang Qi, Hou Peng, Xia Shu, Zhong Shaonan, Zhao Ruiyue, Liang Wanmei, Cui Jiangyu, He Yvlu, Bai Xuejing, Li Youcai, Zhang Ziyi, Fu Zhenli, Liu Shaoyu, Lv Jie, Guo Bingpeng, Fu Yimin, Zhong Huizhen, Zhong Nanshan, Han Qian, Luo Qun, Wang XinLu
Аннотация
PURPOSE: This prospective study aimed to compare the prognostic value of [18F]FAPI-42 (fibroblast activation protein inhibitor) and [18F]FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF).
METHODS: Fifty-two patients with IPF underwent dual-tracer PET/CT. Whole-lung total uptake (wlTU) was quantified for [18F]FAPI-42 and [18F]FDG. PET parameters were correlated with percent predicted forced vital capacity (FVC% pred), percent predicted diffusing capacity for carbon monoxide (DLCO% pred), and the Gender-Age-Physiology (GAP) stage. Immunohistochemical staining (IHC) for FAP and glucose transporter 1 (GLUT-1) was performed (n = 4). The primary endpoint was a composite of all-cause death or lung transplantation (LuTx), analyzed using Kaplan-Meier and Cox proportional hazards models.
RESULTS: In patients with IPF, the median wlTU-FAPI was higher in GAP stage II and III than in GAP stage I (3733 vs. 2985, P = 0.039), whereas wlTU-FDG was not (2247 vs. 2176, P = 0.911). Furthermore, wlTU-FAPI and wlTU-FDG were negatively correlated with DLCO% pred (rs = -0.65, P < 0.001; rs = -0.54, P < 0.001). Notably, wlTU-FAPI was also correlated with FVC% pred (rs = -0.44, P = 0.002), whereas wlTU-FDG did not (P = 0.291). IHC confirmed high FAP and low GLUT-1 expression in fibroblast foci (n = 4). During a median follow-up of 19 (17.0-20.0) months (n = 48), the 13 patients reached the composite endpoint exhibited higher median wlTU-FAPI (3728 vs. 2888, P = 0.028). Conversely, no significant difference was observed for wlTU-FDG (2261 vs. 2139, P = 0.231). In multivariable Cox regression analysis, wlTU-FAPI emerged as an independent predictor of death or LuTx (hazard ratio [HR] per 1000-unit increase, 4.62; 95% CI, 1.62-13.22; P = 0.004), wheras wlTU-FDG did not (P = 0.782). Kaplan-Meier also demonstrated the prognostic value of wlTU-FAPI (cutoff = 2865, P = 0.018), whereas wlTU-FDG was not significant (cutoff = 2036, P = 0.660).
CONCLUSION: [18F]FAPI-42 PET/CT is a promising noninvasive imaging biomarker for predicting clinical outcomes in IPF. Compared with [18F]FDG PET/CT, [18F]FAPI-42 demonstrated stronger associations with disease severity and adverse clinical outcomes in this prospective cohort. These findings warrant further validation in larger and more diverse IPF populations.
METHODS: Fifty-two patients with IPF underwent dual-tracer PET/CT. Whole-lung total uptake (wlTU) was quantified for [18F]FAPI-42 and [18F]FDG. PET parameters were correlated with percent predicted forced vital capacity (FVC% pred), percent predicted diffusing capacity for carbon monoxide (DLCO% pred), and the Gender-Age-Physiology (GAP) stage. Immunohistochemical staining (IHC) for FAP and glucose transporter 1 (GLUT-1) was performed (n = 4). The primary endpoint was a composite of all-cause death or lung transplantation (LuTx), analyzed using Kaplan-Meier and Cox proportional hazards models.
RESULTS: In patients with IPF, the median wlTU-FAPI was higher in GAP stage II and III than in GAP stage I (3733 vs. 2985, P = 0.039), whereas wlTU-FDG was not (2247 vs. 2176, P = 0.911). Furthermore, wlTU-FAPI and wlTU-FDG were negatively correlated with DLCO% pred (rs = -0.65, P < 0.001; rs = -0.54, P < 0.001). Notably, wlTU-FAPI was also correlated with FVC% pred (rs = -0.44, P = 0.002), whereas wlTU-FDG did not (P = 0.291). IHC confirmed high FAP and low GLUT-1 expression in fibroblast foci (n = 4). During a median follow-up of 19 (17.0-20.0) months (n = 48), the 13 patients reached the composite endpoint exhibited higher median wlTU-FAPI (3728 vs. 2888, P = 0.028). Conversely, no significant difference was observed for wlTU-FDG (2261 vs. 2139, P = 0.231). In multivariable Cox regression analysis, wlTU-FAPI emerged as an independent predictor of death or LuTx (hazard ratio [HR] per 1000-unit increase, 4.62; 95% CI, 1.62-13.22; P = 0.004), wheras wlTU-FDG did not (P = 0.782). Kaplan-Meier also demonstrated the prognostic value of wlTU-FAPI (cutoff = 2865, P = 0.018), whereas wlTU-FDG was not significant (cutoff = 2036, P = 0.660).
CONCLUSION: [18F]FAPI-42 PET/CT is a promising noninvasive imaging biomarker for predicting clinical outcomes in IPF. Compared with [18F]FDG PET/CT, [18F]FAPI-42 demonstrated stronger associations with disease severity and adverse clinical outcomes in this prospective cohort. These findings warrant further validation in larger and more diverse IPF populations.